Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOZHQC)

• DTT Name: P2Y purinoceptor 2 (P2RY2)
• Synonyms: P2Y2; P2U1; P2U receptor; P2U purinoceptor 1; P2U nucleotide receptor; P2RY2; Adenosine P2Y2 receptor
• Gene Name: P2RY2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: P2RY2_HUMAN
• TTD ID: T93515
• Sequence:
  MAADLGPWNDTINGTWDGDELGYRCRFNEDFKYVLLPVSYGVVCVPGLCLNAVALYIFLC
  RLKTWNASTTYMFHLAVSDALYAASLPLLVYYYARGDHWPFSTVLCKLVRFLFYTNLYCS
  ILFLTCISVHRCLGVLRPLRSLRWGRARYARRVAGAVWVLVLACQAPVLYFVTTSARGGR
  VTCHDTSAPELFSRFVAYSSVMLGLLFAVPFAVILVCYVLMARRLLKPAYGTSGGLPRAK
  RKSVRTIAVVLAVFALCFLPFHVTRTLYYSFRSLDLSCHTLNAINMAYKVTRPLASANSC
  LDPVLYFLAGQRLVRFARDAKPPTGPSPATPARRRLGLRRSDRTDMQRIEDVLGSSEDSR
  RTESTPAGSENTKDIRL
• Function: Receptor for ATP and UTP coupled to G-proteins thatactivate a phosphatidylinositol-calcium second messenger system. The affinity range is UTP = ATP > ATP-gamma-S >> 2-methylthio-ATP = ADP.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  Surfactant metabolism (R-HSA-5683826)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diquafosol	DM64QG9	Dry eye disease	9E1Z	Phase 3	[1]
INS-37217	DMF93RQ	Cystic fibrosis	CA25	Phase 2	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INS 316	DMTHMEI	Lung cancer	2C25.0	Discontinued in Phase 3	[2]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-thioUTP	DMJZ5V0	Discovery agent	N.A.	Investigative	[3]
4-thio-UTP	DM7YOXW	Discovery agent	N.A.	Investigative	[4]
5BrUTP	DMEVRH4	Discovery agent	N.A.	Investigative	[5]
Acid blue 25	DMCU6XV	Discovery agent	N.A.	Investigative	[6]
AR-C118925XX	DMQCPXL	Discovery agent	N.A.	Investigative	[7]
AR-C126313	DMP1EWV	Discovery agent	N.A.	Investigative	[8]
MDT-006	DMSF4UI	Constipation	DD91.1	Investigative	[9]
MRS2698	DM7EZBU	Discovery agent	N.A.	Investigative	[8]
MRS2768	DMO5J39	Discovery agent	N.A.	Investigative	[10]
PSB-0963	DMBDVJ1	Discovery agent	N.A.	Investigative	[6]
PSB-716	DMS2V0P	Discovery agent	N.A.	Investigative	[11]
PSB1114	DMR9HYI	Discovery agent	N.A.	Investigative	[12]
RB 2	DMCEFUW	Discovery agent	N.A.	Investigative	[11]
SB-416	DMJW72O	Discovery agent	N.A.	Investigative	[11]
UTPgammaS	DMKLB4O	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lung cancer	2C82	Lung tissue	7.03E-10	0.14	0.52
Irritable bowel syndrome	DD91.0	Rectal colon tissue	2.62E-01	-0.2	-0.27

References

• [1] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [2] Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study. Pediatr Pulmonol. 2001 Aug;32(2):122-8.
• [3] Synthesis and structure-activity relationships of uracil nucleotide derivatives and analogues as agonists at human P2Y2, P2Y4, and P2Y6 receptors. J Med Chem. 2006 Nov 30;49(24):7076-87.
• [4] P2 receptors activated by uracil nucleotides--an update. Curr Med Chem. 2006;13(3):289-312.
• [5] Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate. Br J Pharmacol. 1995 Sep;116(1):1619-27.
• [6] Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. J Med Chem. 2010 Mar 11;53(5):2076-86.
• [7] Nucleotide-mediated mucin secretion from differentiated human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2004 Oct;31(4):446-55.
• [8] Molecular modeling of the human P2Y2 receptor and design of a selective agonist, 2'-amino-2'-deoxy-2-thiouridine 5'-triphosphate. J Med Chem. 2007 Mar 22;50(6):1166-76.
• [9] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 324).
• [10] Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists. Bioorg Med Chem. 2008 Jun 15;16(12):6319-32.
• [11] Combinatorial synthesis of anilinoanthraquinone derivatives and evaluation as non-nucleotide-derived P2Y2 receptor antagonists. Bioorg Med Chem Lett. 2008 Jan 1;18(1):223-7.
• [12] Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors. J Med Chem. 2011 Apr 28;54(8):2878-90.